Exoskeletal-assisted Walking to Improve Mobility, Bowel Function and Cardio-Metabolic Profiles in Persons With SCI

Study Design Research design: A Phase III randomized clinical trial (RCT) will be performed
using a crossover design and employing an exoskeletal-assisted walking intervention. The
experimental arm will be compared to a usual activities (UA) arm, as the control, in 64
persons with chronic SCI (>6 month post injury) who are wheelchair-dependent for outdoor
mobility in the community. Eligible participants will be randomized (within site) to one of
two groups for 12 weeks (three months): Group 1 (n=32) will receive exoskeletal-assisted
walking (WALK) first for 12 weeks then crossover UA for a second 12 weeks; Group 2 (n=32)
will receive UA first for 12 weeks then cross-over to the WALK arm for 12 weeks of training.
The WALK arm will consist of supervised exoskeletal-assisted walking training, three sessions
per week (4-6 h/week) for 36 sessions for their second 12-week period. The UA arm will
consist of identification of usual activities for each participant, encouragement to continue
with these activities and attention by study team members throughout the 12-week UA arm.
These activities will be recorded in a weekly log. A fixed answer format will be used to
capture this information.

Rationale for intervention to be studied: This research design has several advantages. Group
1 will serve as the intervention follow-up to assess retention or non-retention of change due
to the intervention on the outcome variables. Group 2 will serve as a lead-in to assess
stability of the outcome variables prior to the intervention. Additionally, because of
tremendous variability in the SCI population and difficulty with case-control matching, the
cross-over design will help to control for variability between participants because each
participant will serve as their own control. Veterans and nonveterans with SCI generally do
not receive further structured rehabilitation once they have completed the acute and
sub-acute phases of their rehabilitation. As such, the usual lifestyle activities have been
chosen as the control for this study. Dr. Spungen has discussed the optimal control for an
exoskeletal-assisted walking program. She has consulted with the Chiefs of several SCI
Services in both the VA and non-VA rehabilitation hospitals. A case-controlled, matched RCT
study would be strongest with two interventions: exoskeletal-assisted walking compared with
any other form of physical activity such as robotically assisted body weight supported
treadmill training (Lokomat), body weight supported treadmill training, arm ergometry etc.
However, there are two considerations that make this type of study not feasible. One is that
it would be extremely difficult to case-control match for independent variables within site,
and the second is that most participants would likely not agree to participate if there was a
50% chance they would not get the exoskeletal-assisted walking arm. In order to control for
an attention effect, participants in the UA arm will keep weekly activity logs and be
contacted by phone calls from the study team to receive attention and encouragement to
continue participation in the UA of their choice. In order to control for attention aspects
of this type of study, participants will also make in person twice monthly visits to their
sites during the UA arm. During these visits, study team staff will review their UA logs and
administers the 10Q BFS and BSS.

Because the achievement of improved secondary medical outcomes is likely dependent on the
ability to walk in the exoskeletons, the primary outcome will be achievement of mobility
skills in the exoskeletal devices. It has not been demonstrated in a large sample that people
with SCI can use the device as described by the pilot data. Secondary outcomes will be change
in fat mass and bowel function. Exploratory outcomes will be change in cardiovascular and
autonomic measures and quality of life surveys [using the newly validated SCI quality of life
(SCI-QOL) tool for bowel, bladder and five emotional domains]21,50.

Description of walking in the ReWalk: The ReWalk exoskeletal system requires the user to
actively shift their body appropriately over their legs in order to maintain balance on the
stance leg allowing the swing leg to clear the floor. This is accomplished with coordinated
movements involving the upper extremity muscles in the trunk, arms, shoulder, back, neck, and
head for the body to maintain balance dynamically as the system assists the legs to move in a
normal walking pattern. Balance is maintained with the use of Loftstrand crutches. A mode
selector, which is worn on the wrist, is used to select "walk mode" once the person is stable
during standing. Following walk mode selection, the user shifts onto the left leg and
slightly forward so that the right leg is offloaded. The tilting/leaning action triggers the
device to swing the right leg forward and the user weight shifts so that their trunk is over
the right leg as they step onto the right foot. This will then initiate the left leg to swing
forward; the use weight shifts onto it and continuous walking is achieved if this coordinated
weight shifting and stepping onto each leg is continued. The unit will stop walking in two
ways. If the user does not shift their weight onto the front foot, then the ReWalk will time
out after two seconds and return to the standing position. The second way is if the person
does not shift their weight appropriately to have the swing leg clear the floor. This will
cause the leg to have some additional external force that the ReWalk will sense and cause the
system to return to standing mode. The stepping and walking gait pattern of the ReWalk is
very similar to normal walking51. The gait pattern settings in the ReWalk can be preset in
order to increase or decrease the step length, speed of the step and/or the amount of foot
clearance the person will have during walking, permitting a velocity of 0.10 to 0.80 m/s.

In order to successfully accomplish walking with the ReWalk, considerable coordination
between the upper extremity muscles in the trunk, arms, shoulder, back, neck, and head is
needed in conjunction with dynamic standing balance. A specific pattern of trunk positioning,
crutch placement and weight shifting is needed. To prepare for walking, the user must attain
a stable standing position with the crutches placed slightly in front of him/her. To begin
walking, the user must shift their weight onto the left foot to unweight the right foot. The
right foot steps forward first, and this is initiated when the user slightly leans forward,
by bringing the crutches forward, away from the stepping leg to allow it to swing forward and
clear the floor. As the stepping leg moves forward and extends toward the ground, the user
shifts weight forward, stepping onto that leg and then sequentially brings the crutches
forward for the next step. Immediately after the weight is shifted, the user must straighten
his/her posture with their body perpendicular to the ground before leaning forward to
initiate the next step. This is similar to a normal walking pattern. As the leg contralateral
to the initial step leg swings forward, the participant must shift the crutches away from
that leg to allow it to step forward. This process is repeated for continued walking.

Description of walking in the Ekso: The users are progressed through a series of steps to
participate in over ground ambulation. The first method, called FirstStep. This is when the
trainer triggers the step by using a controller while verbally cueing the participant that
the device is taking a step. The second method, called ActiveStep is when the user to
initiates the stepping action by pressing a button on a pair of instrumented crutches for
each step. The last method, called ProStep, is when the user shifts their weight lateral and
forward onto the front foot, until sensors indicate when an appropriate shift has been
performed. The stepping pattern can be adjusted to change the step time and step length. The
trajectory of the foot allows for foot clearance similar to a marching pattern. The device
has the ability for provide some abduction and plantar/dorsi flexion positioning. This device
has the ability to alter the stepping, which would allow the user to take faster or slower
steps with a longer or shorter stride length, thus permitting a walking velocity of 0.10 to
0.45 m/s. Stopping is achieved by holding a stationary position and by not activating
sensors. The Ekso allows for varying robot-assist levels that can be decrease or increased
bilaterally. The robot assistance can operate will full or variable assist, dependent on the
level of function of the individual.

Inclusion Criteria:

- Males and females, between 18-70 years old

- Traumatic or non-traumatic paraplegia >6 months in duration

- SCI motor deficit at any level

- Unable to ambulate faster than 0.17 m/s on level ground with or without an assistive
device and are wheelchair-dependent for community mobility

- Height 160 to 190 cm (63-75 in or 5'3" to 6'3" ft)

- Weight <100 kg (<220 lb)

- Able to hold the crutches

- Able to sign informed consent.

Exclusion Criteria:

- Diagnosis of neurological injury other than SCI including:

- Multiple sclerosis, Stroke, Cerebral Palsy, Amyotrophic lateral sclerosis, Traumatic
Brain injury, Spina bifida, Parkinson's disease, or

- Other neurological condition that the study physician considers in his/her clinical
judgment to be exclusionary

- Severe concurrent medical disease, illness or condition

- Recent lower extremity fracture within the past 2 years

- DXA results indicating a t-score below -3.5 at the femoral neck or the total proximal
femur bone and knee BMD <0.60 gm/cm2

- Diagnosis of heterotropic ossification of the lower extremities which affect range of
motion or proper measurement of BMD measurements

- Significant contractures defined as flexion contracture limited to 35º at the hip and
20º at the knee

- Untreated hypertension (SBP>140, DBP>90 mmHg)

- Symptomatic orthostatic hypotension with standing that does not resolve after attempts
at upright posture that were made over several days, and standing by the participant
is deemed to pose a health risk, as determined by a physician, because of symptomatic
orthostatic hypotension

- Systemic or peripheral infection

- Atherosclerosis, congestive heart failure, or history of myocardial infarction;

- Trunk and/or lower extremity pressure ulcers

- Severe spasticity (defined by an Ashworth score of >4.0 or clinical impression of the
study physician or physical therapist)

- Significant contractures defined as flexion contracture limited to 25º at the hip and
knee

- Diagnosis of heterotropic ossification of the lower extremities which affect range of
motion or proper measurement of BMD measurements

- Psychopathology documentation in the medical record or history of that may conflict
with study objectives

- Pregnancy and/or lactating females

- Brain injury with score on mini-mental status examination less than 26

- Diagnosis of coronary artery disease that precludes moderate to intense exercise

- Deep vein thromboses in lower extremities of less than 6 months duration

- Other illness, that the study physician considers in his/her clinical judgment to be
exclusionary.